3076
J. Gonza´lez-Sab´ın et al. / Tetrahedron: Asymmetry 16 (2005) 3070–3076
C, 72.84; H, 8.56; N, 5.66. Found: C, 72.81; H, 8.60; N,
5.65.
Acknowledgments
We thank Novo Nordisk Co. for the generous gift of the
CAL-B. This work has been supported by MEC (Spain;
Project MEC-04-CTQ-04185). J.G.-S. thanks the Span-
ish MEC for a predoctoral fellowship.
4.5.7.
(1S,2R)-2-Phenylcyclopropanamine
(1S,2R)-
20
5. ½aꢁD = ꢀ105.1 (c 1.0, CHCl3); ee = 96%. Lit.14 for
25
(1S,2R)-(ꢀ)-5: ½aꢁD = ꢀ115.8 (c 1.13, CHCl3);
ee = >99%.
4.5.8.
(1R,2S)-19. White solid, mp = 100–101.5 ꢁC; ½aꢁD
ꢀ76.2 (c 0.66, CHCl3); ee = 69%. IR (CH2Cl2) 3424,
1644 cmꢀ1 1H NMR (200 MHz): major conformer
(1R,2S)-N-(2-Phenylcyclopropyl)acetamide
References
20
=
1. (a) McGrath, W. R.; Kuhn, W. L. Arch. Int. Pharmaco-
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;
d = 1.05–1.20 (m, 2H), 1.95 (s, 3H, CH3), 1.95–2.10
(m, 1H), 2.89 (dt, 1H, J = 7.8 and 3.7 Hz), 6.75(br s,
1H, NH), 7.05–7.26 (m, 5H, Ph); minor conformer
d = 1.20–1.30 (m, 2H), 1.95–2.10 (m, 1H), 2.12 (s, 3H,
CH3), 2.73 (m, 1H), 6.21 (br s, 1H, NH), 7.05–7.26
(m, 5H, Ph); 13C NMR (75.5 MHz): major conformer
d = 15.95 (CH2), 22.84 (CH3), 24.21 (CH), 32.07 (CH),
126.06 (CH), 126.23 (CH), 128.16 (CH), 140.44 (C),
171.46 (C@O); minor conformer d = 17.14 (CH2),
21.09 (CH3), 26.36 (CH), 34.24 (CH), 125.41 (CH),
126.06 (CH), 128.41 (CH), 140.44 (C), 171.46 (C@O);
MS (ESI+), m/z (%) = 176 ([M+H]+, 5), 198
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C, 75.40; H, 7.48; N, 7.99. Found: C, 75.49; H, 7.40;
N, 8.02.
´
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E.; Escalante, J.; Leon-Romo, J. L.; Reyes, A. Tetra-
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3551; (b) Gonzalez-Sabın, J.; Gotor, V.; Rebolledo, F.
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K.; Kim, M. J.; Ahn, Y.; Kim, M.-J. Org. Lett. 2001, 3,
4.6. Assignment of the absolute configuration
The absolute configuration of the remaining amines 3–5
obtained in the enzymatic processes were determined by
comparison of the sign of their specific rotations with
those reported. Consequently, the absolute configuration
for the amides was also established. In all cases, lipases
tested following KazlauskasÕ rule showed the (1R)-enan-
tiomer of the substrate being preferentially transformed.
´
4099–4101; (d) Lopez-Serrano, P.; Jongejan, J. A.; Rant-
wijk, F.; Sheldon, R. A. Tetrahedron: Asymmetry 2001, 12,
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´
´
´
6. Gonzalez-Sabın, J.; Gotor, V.; Rebolledo, F. Tetrahedron:
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4.7. Determination of the enantiomeric excesses
The enantiomeric excess for each optically active com-
pound isolated from the enzymatic reactions was deter-
mined by HPLC. Acetamides 15, 17, and 19 were
directly analyzed using a Chiralcel OD column. Amines
3–5 were transformed into the corresponding acetamides
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chloride (1.2 equiv), DMAP (1.0 equiv) in dichloro-
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oxyacetamides, these were previously hydrolyzed (3 M
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4.8. HPLC method
A Chiralcel OD column was used in all cases. Hexane–
isopropyl alcohol (H–IPA) mixtures were employed as
eluents, with a flow value of 0.8 mL/min. For 15: H–
IPA, 92:8; T = 20 ꢁC; tR = 10.01 (1R,2S) and 11.29
(1S,2R) min; RS = 2.4. For 17: H–IPA, 92:8;
T = 20 ꢁC; tR = 12.96 (1R,2R) and 20.44 (1S,2S) min;
RS = 7.0. For 19: H–IPA, 90:10; T = 30 ꢁC; tR = 19.34
(1R,2S) and 23.29 (1S,2R) min; RS = 2.5.
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